amfAR, The Foundation for AIDS Research

Envisioning an AIDS Vaccine

by Jeffrey Laurence, M.D., and Rowena Johnston, Ph.D.

July 18, 2007—Progress in AIDS vaccine development remains frustratingly slow, but amfAR-funded scientists such as research fellow Dr. Sang-Moo Kang, who described his research in the June issue of the journal Virology, are bringing us closer to realizing that elusive goal.

Many scientists believe that to be effective, vaccines will need to elicit strong and durable immune responses from both killer T cells and antibodies. The former are particularly effective at ridding the body of cells that have been infected by a virus, while the latter can also destroy virus particles that have not yet associated with cells.

Researchers interested in designing an AIDS vaccine, such as Dr. Kang, are striving to find ways to activate both of these components of the immune defense against viruses. Last year we highlighted the vaccine research of amfAR scientist Dr. Richard Kornbluth, who is developing novel immune boosters or “molecular adjuvants.” These products have the capacity to recruit and activate specialized types of immune cells known as dendritic cells (DCs). Located at strategic sites in the body where HIV and other infections enter, DCs capture and process proteins from these invaders, then carry them to appropriate sites where they activate immune defenses. Importantly, DCs have the potential to activate aspects of killer T cell and antibody function.

Working at the Emory Vaccine Center in Atlanta, Dr. Kang built on this type of approach. Viruses, including HIV, are potent stimulators of DCs. Given that safety considerations would not permit the use of a whole HIV virus as a vaccine, or even a weakened version of it, Dr. Kang reasoned that the best way to stimulate DCs might be to use as much of the natural virus as possible. He designed an AIDS virus from which he removed those genes that permit it to grow and do harm, but added in a gene that could promote the growth of DCs that this virus-like structure might encounter. His creation, known as VLP-FL, is a virus-like particle (VLP) containing core and envelope genes from HIV, along with a gene for the DC growth factor Flt3 ligand (FL).

Injected into mice, VLP-FL not only increased dendritic cells but stimulated a myriad of immune cells, all exhibiting characteristics that suggested they were primed to attack HIV. Indeed, when Dr. Kang compared normal virus-like particles to those that had Flt3 ligand added to them, he found that in the blood of mice immunized with VLP-FL, the level of antibody against the AIDS virus coat, Env, was twice that of mice receiving only the VLP. Because Env sits on the outside of the virus and is therefore the most accessible virus protein, a vaccine that could generate antibodies against Env would probably be the most effective way to use antibodies to disable the virus. Dr. Kang’s work, along with that of many amfAR-funded scientists, is paving the way toward a crucial HIV prevention tool, an AIDS vaccine.

Dr. Laurence is amfAR’s senior scientific consultant and Dr. Johnston is amfAR’s vice president for research.